Sermorelin: the first 29 amino acids of GHRH and the pediatric growth studies

Sermorelin is the first 29 amino acids of human growth hormone-releasing hormone (GHRH), written GHRH(1-29)-NH2 in the older literature. The natural hormone has 44 residues. The studies below, from 1987 to 1995, tested the fragment in children, and they remain a useful record of what a short GHRH analogue does over months of treatment.

Where it acts

Because sermorelin works upstream of the pituitary, the studies treat it as a way to ask whether stimulating the body's own GH release can replace GH itself in children who lack the hormone.

Eighteen GH-deficient children, 1987

A 1987 paper in The Lancet treated 18 prepubertal children with growth hormone deficiency with a GHRH(1-29)-NH2 analogue by subcutaneous injection. Height velocity rose in 12 of them, and 8 had a worthwhile response, with gains of 2.7 to 11.2 cm per year in the first 6 months that held for 6 to 18 months.

Among the 14 children who had earlier received human GH, growth on GH correlated with growth on GHRH, although 4 of them slowed down on GHRH for reasons the authors could not explain. A peak GH response above 30 mU/l in an intravenous GHRH test before treatment predicted a good growth response. Antibodies to GHRH appeared in 14 children without any apparent effect on growth or on GH responses. The authors called the treatment an alternative to GH for some children.

Head to head with growth hormone, 1993

A randomized comparison enrolled 60 children with hypothalamic growth hormone deficiency into three equal groups: two doses of GHRH(1-29)-NH2 by continuous infusion, or GH. Growth in the GH group was significantly better than in the other two (P < 0.01). The two GHRH groups did not differ from each other.

IGF-I rose at first on GHRH and then fell back to pretreatment levels. All 20 children on the higher dose and 19 of 20 on the lower dose developed antibodies to GHRH, and these had almost disappeared nine months after stopping. Antibody levels did not correlate with height gain. No serious side effects were seen, and three children had mild irritation at the injection site. The authors concluded that this treatment, or a depot form of it, was unlikely to be as effective as GH for promoting growth.

Short children with normal GH, 1995

A 1995 paper in Acta Paediatrica treated seven children with idiopathic short stature, heights well below the third percentile, and normal GH levels. Treatment stopped if growth did not increase by more than 2 cm per year over the pretreatment rate. Two children stopped at 12 months and five continued to 24 months. The authors reported that some of these patients grew well in the first two years. With seven children and no control group, the result shows that a response is possible and does not show how often it occurs.

Reading these results

The older pediatric literature has a few lessons for anyone reading the sermorelin papers.

• Compare with the standard. In the randomized trial, GH produced faster growth than the GHRH fragment.
• Antibodies were common. They did not correlate with growth in these studies and faded after treatment stopped.
• The population is narrow. Every paper studied children, mostly with GH deficiency, and none studied healthy adults.
• The trials are small and old. They predate current trial standards, so they describe pharmacology more than they settle questions of benefit.

A 29-residue peptide like this has a calculated average mass of about 3,358 Da, which is the figure the mass spectrum on a certificate of analysis should show.